Prymnesin-2

Last updated
Prymnesin-2
Prymnesin-2 corrected.svg
Names
IUPAC name
(11S)-1-[(2R,3R,4R,5S,6R)-6-[(2R,3S,4R,4aR,6R,8aR)-6-[(2R,3S,4aR,6S,8R,8aS)-6-[(2R,3R,4aR,6S,8R, 8aR)-6-[(2S,3S,4aS,6R,8aR)-2-[(1S,3R,5S,7S,10S,12R,14S,16S,21R,22R)-7-[(1Z,3Z,6R,8Z,10Z,18Z)-6-amino-19-chlorononadeca-1,3,8,10,18-pentaen-12,16-diynyl]-22-hydroxy-2,6,11,15,20-pentaoxapentacyclo[12.9.0.03,12.05,10.016,21]tricosan-19-yl]-3-methyl-2,3,4,4a,6,7,8,8a-octahydropyrano[3,2-b]pyran-2-yl]-8-chloro-3-hydroxy-2,3,4,4a,6,7,8,8a-octahydropyrano[3,2-b]pyran-2-yl]-11-chloro-3-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxyhexadeca-13,15-diyne-2,4,6,7,8,9,10-heptol
Other names
PRM2 [1]
Identifiers
3D model (JSmol)
PubChem CID
  • InChI=1S/C96H136Cl3NO35/c1-3-4-15-23-47(98)75(109)79(113)80(114)76(110)49(102)35-50(103)88(135-96-85(119)78(112)74(43-101)132-96)51(104)38-70-77(111)81(115)82(116)94(131-70)95-84(118)83(117)93-62(130-95)31-30-61(129-93)90-54(107)39-72-87(133-90)48(99)34-71(126-72)91-55(108)40-73-92(134-91)53(106)36-64(125-73)57-26-27-58-63(121-57)33-44(2)86(127-58)59-28-29-60-89(128-59)52(105)37-65-67(123-60)42-68-69(124-65)41-66-56(122-68)25-24-46(120-66)22-18-14-17-21-45(100)20-16-12-10-8-6-5-7-9-11-13-19-32-97/h1,8,10,12,14,16-19,22,32,44-96,101-119H,7,9,20-21,23-31,33-43,100H2,2H3/b10-8+,16-12+,17-14+,22-18+,32-19+/t44-,45+,46+,47-,48+,49?,50?,51?,52+,53+,54-,55+,56-,57+,58+,59?,60-,61?,62+,63-,64?,65-,66-,67-,68+,69+,70+,71?,72+,73+,74+,75?,76?,77-,78+,79?,80?,81+,82-,83+,84-,85+,86-,87+,88?,89+,90+,91+,92+,93-,94?,95+,96+/m0/s1
    Key: WCHCDYFGLWOFCV-GUPVPWLLSA-N
  • C[C@H]1C[C@]2([H])O[C@@H](C3C[C@H]([C@@]4([H])O[C@@H](C5C[C@H]([C@@]6([H])O[C@@H](C7CC[C@@]8([H])O[C@@H](C9O[C@@H]([C@@H]([C@H]([C@@H]9O)O)O)CC(C(C(CC(C(C(C(C([C@H](CC#CC#C)Cl)O)O)O)O)O)O)O[C@H]%10O[C@@H]([C@H]([C@H]%10O)O)CO)O)[C@H]([C@H]([C@@]8([H])O7)O)O)[C@H](C[C@@]6([H])O5)O)Cl)[C@@H](C[C@@]4([H])O3)O)O)CC[C@@]2([H])O[C@@H]1C%11CC[C@]%12([H])O[C@@]%13([H])C[C@@]%14([H])O[C@@]%15([H])CC[C@@H](/C=C/C=C/C[C@@H](C/C=C/C=C/C#CCCC#C/C=C/Cl)N)O[C@@]%15([H])C[C@@]%14([H])O[C@@]%13([H])C[C@H]([C@@]%12([H])O%11)O
Properties
C96H136Cl3NO35
Molar mass 1970.47 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Prymnesin-2 is an organic compound that is secreted by the haptophyte Prymnesium parvum . It belongs to the prymnesin family and has potent hemolytic and ichthyotoxic properties. In a purified form it appears as a pale yellow solid. [2] P. parvum is responsible for red harmful algal blooms worldwide, causing massive fish killings. When these algal blooms occur, this compound poses a threat to the local fishing industry. This is especially true for brackish water, as the compound can reach critical concentrations more easily. [2]

Contents

Structure and reactivity

The structural formula of prymnesin-2 is: C96H136Cl3NO35. The compound exhibits multiple chiral centers. The molecule is amphoteric, which means that it can act both as base and an acid. This is because all 16 hydroxyls, except for one at C32, are concentrated on carbons C48-84, and there α-L-xylofuranose moiety at C77. [1] This might lead to interaction with biomembranes, which is thought to be the basis of its toxicity. [2] The difference between prymnesin-1 and prymnesin-2 is the glycosidic residues: L-arabinose, D-galactose and D-ribose, yet prymnesin-2 and prymnesin-1 show comparable activities. Prymnesins also have unique features: The possession of only one methyl, but three chlorine atoms, four C-C triple bonds, sugars and an amino group. [3]

Biosynthesis

Prymnesin-1 and prymnesin-2 are both are derived from acetate-related (i.e. polyketide) metabolism, based on knowledge about the structure of the prymnesins. In general primary and secondary metabolites such as fatty acids, polyketides and non-ribosomal peptides are synthesised by the acetate pathway. [4] In 2024 the backbone of A-type prymnesins like prymnesin-2 was reported to be made by giant polyketide synthase enzymes dubbed the "PKZILLAs". [5]

Mechanism of action

The mechanism of action of prymnesin-2 remains to be determined. [3] Prymnesin-2 and prymnesin-1 show comparable activities. Prymnesin-2 has shown multiple functionalities, such as potent hemolytic activity and diverse biological activities, such as mouse lethality, ichthyotoxicity and activity inducing Ca+2 influx into cultured cells. The hemolytic potency of prymnesin-2 exceeds that of plant saponin by 50.000 times. [6]

Prymnesin-2 causes hemolysis by direct interaction between toxin and cell surface. Partly due to interaction with cellular lipids, mainly to interaction with a specific binding site on the blood cell surface. This is supported by the observation of competitive inhibition by the prymnesin-2 analogues, which assume the presence of a specific binding site on the blood cell surface. Also the process of toxin molecule aggregation may be involved in the main mechanism of the haemolytic activity. [6]

Toxicity

Prymnesin-2 is an ichthyotoxic compound with the ability to hemolyze blood. 2.5 nM is needed for a 50% hemolysis rate of a 1% rat blood cell suspension, and 9 nM is enough for killing freshwater fish. The hemolytic and ichthyotoxic properties increase when the pH of the solution rises from 7 to 8. [7] Prymnesin-2 causes calcium ion influx into C6 rat glioma cells at a concentration of 70 nM. [8]

Besides the lytic effect on blood cells, hepatocytes, Hela cells and artificial liposomes are affected by prymnesin-2.

As seen in the table below, prymnesin-2 is highly hemolytic for blood cells of different animal species, even when compared to the already highly hemolytic toxin saponin.

Table1. Sensitivities of blood cells from different animal species
Prymnesin-2 (nM)Saponin (nM)Relative to saponin
Mouse2.5170006800
Rabbit1.7150008800
Dog0.52500050000
Sheep0.62300038000
Chicken1.9170008900
Carp1.6115007200

Effects on animals

In the US, the first recorded P. parvum bloom occurred in 1985 in a semi-arid region of the country (Pecos River, Texas). [9] Since then, the incidence of P. parvum blooms dramatically increased in the US, where the organism has invaded lakes and rivers throughout southern regions and most recently into northern regions. The magnitude of P. parvum blooms are also increasing over the past decade compared to 30 years ago, with massive fish killings as result. [10] [11] [12]

See also

Related Research Articles

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<span class="mw-page-title-main">Maitotoxin</span> Chemical compound

Maitotoxin (MTX) is an extremely potent biotoxin produced by Gambierdiscus toxicus, a dinoflagellate species. Maitotoxin has been shown to be more than one hundred thousand times as potent as VX nerve agent. Maitotoxin is so potent that it has been demonstrated that an intraperitoneal injection of 130 ng/kg was lethal in mice. Maitotoxin was named from the ciguateric fish Ctenochaetus striatus—called "maito" in Tahiti—from which maitotoxin was isolated for the first time. It was later shown that maitotoxin is actually produced by the dinoflagellate Gambierdiscus toxicus.

Prymnesium parvum is a species of haptophyte. The species is of concern because of its ability to produce the phycotoxin prymnesin. It is a flagellated alga that is normally found suspended in the water column. It was first identified in North America in 1985, but it is not known if it was introduced artificially or missed in previous surveys. Toxin production mainly kills fish and appears to have little effect on cattle or humans. This distinguishes it from a red tide, which is an algal bloom whose toxins lead to harmful effects in people. Although no harmful effects are known, it is recommended not to consume dead or dying fish exposed to a P. parvum bloom.

<span class="mw-page-title-main">Halomon</span> Chemical compound

Halomon is a polyhalogenated monoterpene first isolated from the marine red algae Portieria hornemannii. Halomon has attracted research interest because of its promising profile of selective cytotoxicity that suggests its potential use as an antitumor agent.

Brevetoxin (PbTx), or brevetoxins, are a suite of cyclic polyether compounds produced naturally by a species of dinoflagellate known as Karenia brevis. Brevetoxins are neurotoxins that bind to voltage-gated sodium channels in nerve cells, leading to disruption of normal neurological processes and causing the illness clinically described as neurotoxic shellfish poisoning (NSP). Although brevetoxins are most well-studied in K. brevis, they are also found in other species of Karenia and at least one large fish kill has been traced to brevetoxins in Chattonella.

<span class="mw-page-title-main">Cylindrospermopsin</span> Chemical compound

Cylindrospermopsin is a cyanotoxin produced by a variety of freshwater cyanobacteria. CYN is a polycyclic uracil derivative containing guanidino and sulfate groups. It is also zwitterionic, making it highly water soluble. CYN is toxic to liver and kidney tissue and is thought to inhibit protein synthesis and to covalently modify DNA and/or RNA. It is not known whether cylindrospermopsin is a carcinogen, but it appears to have no tumour initiating activity in mice.

<i>Gambierdiscus toxicus</i> Species of protist

Gambierdiscus toxicus is a species of photosynthetic unicellular eukaryote belonging to the Alveolata, part of the SAR supergroup. It is a dinoflagellate which can cause the foodborne illness ciguatera, and is known to produce several natural polyethers including ciguatoxin, maitotoxin, gambieric acid, and gambierol. The species was discovered attached to the surface of brown macroalgae.

<span class="mw-page-title-main">Prymnesin-1</span> Chemical compound

Prymnesin-1 is a chemical with the molecular formula C
107H
154Cl
3NO
44. It is a member of the prymnesins, a class of hemolytic phycotoxins made by the alga Prymnesium parvum. It is known to be toxic to fish, causing mass fish deaths around the world, including in Texas and England, or in 2022 in the border region of Germany and Poland (Oder).

Euglenophycin is an ichthyotoxic compound isolated from Euglena sanguinea, a protist of the genus Euglena. It exhibits anticancer and herbicidal activity in vitro.

Ichthyotoxins are compounds which are either toxic to fish, or are toxins produced by fish. The former include the algae-produced euglenophycin and prymnesins, which can cause large-scale fish deaths. The latter includes ostracitoxin, produced by boxfish. Many toxin-producing algal species can be found both in marine and fresh water environments when the algae are in bloom. Ichthyotoxic poisoning in humans can cause symptoms ranging in severity dependent on how much toxin was consumed. The symptoms of an ichthyotoxin poisoning from fish venoms can include headache, vomiting, diarrhea, dizziness, and drop in blood pressure.

<span class="mw-page-title-main">Azaspiracid</span> Chemical compound

Azaspiracids (AZA) are a group of polycyclic ether marine algal toxins produced by the small dinoflagellate Azadinium spinosum that can accumulate in shellfish and thereby cause illness in humans.

Dinotoxins are a group of toxins which are produced by flagellate, aquatic, unicellular protists called dinoflagellates. Dinotoxin was coined by Hardy and Wallace in 2012 as a general term for the variety of toxins produced by dinoflagellates. Dinoflagellates are an enormous group of marine life, with much diversity. With great diversity comes many different toxins, however, there are a few toxins that multiple species have in common.

<i>Cochlodinium polykrikoides</i> Species of single-celled organism

Cochlodinium polykrikoides is a species of red tide producing marine dinoflagellates known for causing fish kills around the world, and well known for fish kills in marine waters of Southeast Asia. C. polykrikoides has a wide geographic range, including North America, Central America, Western India, Southwestern Europe and Eastern Asia. Single cells of this species are ovoidal in shape, 30-50μm in length and 25-30μm in width.

<span class="mw-page-title-main">Antillatoxin</span> Chemical compound

Antillatoxin (ATX) is a potent lipopeptide neurotoxin produced by the marine cyanobacterium Lyngbya majuscula. ATX activates voltage-gated sodium channels, which can cause cell depolarisation, NMDA-receptor overactivity, excess calcium influx and neuronal necrosis.

<span class="mw-page-title-main">Debromoaplysiatoxin</span> Chemical compound

Debromoaplysiatoxin is a toxic agent produced by the blue-green alga Lyngbya majuscula. This alga lives in marine waters and causes seaweed dermatitis. Furthermore, it is a tumor promoter which has an anti-proliferative activity against various cancer cell lines in mice.

Gambierol is a marine polycyclic ether toxin which is produced by the dinoflagellate Gambierdiscus toxicus. Gambierol is collected from the sea at the Rangiroa Peninsula in French Polynesia. The toxins are accumulated in fish through the food chain and can therefore cause human intoxication. The symptoms of the toxicity resemble those of ciguatoxins, which are extremely potent neurotoxins that bind to voltage-sensitive sodium channels and alter their function. These ciguatoxins cause ciguatera fish poisoning. Because of the resemblance, there is a possibility that gambierol is also responsible for ciguatera fish poisoning. Because the natural source of gambierol is limited, biological studies are hampered. Therefore, chemical synthesis is required.

<span class="mw-page-title-main">Prymnesin-B1</span> Chemical compound

Prymnesin-B1 is a chemical with the molecular formula C
91H
132ClNO
34. It is a member of the prymnesins, a class of ladder-frame polyether phycotoxins made by the alga Prymnesium parvum. It is known to be toxic to fish. It is a so called "B-type" prymnesin, which differ in the number of backbone cycles when compared to A-type prymnesins like prymnesin-2.

Grammistins are peptide toxins synthesised by glands in the skin of soapfishes of the tribes Grammistini and Diploprionini which are both classified within the grouper subfamily Epinephelinae, a part of the family Serranidae. Grammistin has a hemolytic and ichthyotoxic action. The grammistins have secondary structures and biological effects comparable to other classes of peptide toxins, melittin from the bee stings and pardaxins which are secreted in the skin of two sole species. A similar toxin has been found to be secreted in the skin of some clingfishes.

<i>Karlodinium veneficum</i> Species of single-celled organism

Karlodinium veneficum is a species of dinoflagellates belonging to the family Kareniaceae. This species is predominantly inhabiting aquatic environments, particularly in temperate coastal regions.

<span class="mw-page-title-main">Scaritoxin</span> Toxin

Scaritoxin, a potent toxic substance, is a ciguatoxin with molecular formula C60H84O16. Scaritoxin is also referred to as ciguaotoxin 4A, CTX4A. Like other ciguatoxins, CTX4A is produced by dinoflagellate Gambierdiscus toxicus and isolated from poisonous fish.

References

  1. 1 2 Igarashi, Tomoji; Satake, Masayuki; Yasumoto, Takeshi (1999). "Structures and Partial Stereochemical Assignments for Prymnesin-1 and Prymnesin-2: Potent Hemolytic and Ichthyotoxic Glycosides Isolated from the Red Tide AlgaPrymnesium parvum". Journal of the American Chemical Society. 121 (37). American Chemical Society (ACS): 8499–8511. doi:10.1021/ja991740e. ISSN   0002-7863.
  2. 1 2 3 Igarashi, Tomoji; Satake, Masayuki; Yasumoto, Takeshi (1996). "Prymnesin-2: A Potent Ichthyotoxic and Hemolytic Glycoside Isolated from the Red Tide Alga Prymnesium parvum". Journal of the American Chemical Society. 118 (2): 479–480. doi:10.1021/ja9534112.
  3. 1 2 Yasumoto, Takeshi (2001). "The chemistry and biological function of natural marine toxins". The Chemical Record. 1 (3): 228–242. doi:10.1002/tcr.1010. ISSN   1528-0691. PMID   11895121.
  4. ↑ Manning, Schonna R.; La Claire, John W. (2010-03-16). "Prymnesins: Toxic Metabolites of the Golden Alga, Prymnesium parvum Carter (Haptophyta)". Marine Drugs. 8 (3): 678–704. doi: 10.3390/md8030678 . PMC   2857367 . PMID   20411121.
  5. ↑ Fallon, Timothy R.; Shende, Vikram V.; Wierzbicki, Igor H.; Pendleton, Amanda L.; Watervoort, Nathan F.; Auber, Robert P.; Gonzalez, David J.; Wisecaver, Jennifer H.; Moore, Bradley S. (2024-08-09). "Giant polyketide synthase enzymes in the biosynthesis of giant marine polyether toxins". Science. 385 (6709): 671–678. doi:10.1126/science.ado3290. ISSN   0036-8075.
  6. 1 2 Igarashi, T.; Aritake, S.; Yasumoto, T. (1998). "Biological activities of prymnesin-2 isolated from a red tide alga Prymnesium parvum". Natural Toxins. 6 (1): 35–41. doi:10.1002/(SICI)1522-7189(199802)6:1<35::AID-NT7>3.0.CO;2-7. ISSN   1056-9014. PMID   9851510.
  7. ↑ Granéli, Edna; Salomon, Paulo S. (1 February 2010). "Factors Influencing Allelopathy and Toxicity in Prymnesium parvum". JAWRA Journal of the American Water Resources Association. 46 (1): 108–120. Bibcode:2010JAWRA..46..108G. doi:10.1111/j.1752-1688.2009.00395.x. ISSN   1752-1688.
  8. ↑ Morohashi, Akio; Satake, Masayuki; Oshima, Yasukatsu; Igarashi, Tomoji; Yasumoto, Takeshi (2001). "Absolute configuration at C14 and C85 in prymnesin-2, a potent hemolytic and ichthyotoxic glycoside isolated from the red tide alga Prymnesium parvum". Chirality. 13 (9): 601–605. doi:10.1002/chir.1184. ISSN   1520-636X. PMID   11579456.
  9. ↑ James T. L., De La Cruz A.. Prymnesium parvum Carter (Chrysophyceae) as a suspect of mass mortalities of fish and shellfish communities in western Texas, Texas Journal of Science, 1989, vol. 41 (pp. 429-430).
  10. ↑ Roelke, Daniel; Augustine, Sarah; Buyukates, Yesim (2003-11-01). "Fundamental Predictability in Multispecies Competition: The Influence of Large Disturbance". The American Naturalist. 162 (5): 615–623. doi:10.1086/378750. ISSN   0003-0147. PMID   14618539. S2CID   19980618.
  11. ↑ Buyukates, Yesim; Roelke, Daniel (2005-10-01). "Influence of Pulsed Inflows and Nutrient Loading on Zooplankton and Phytoplankton Community Structure and Biomass in Microcosm Experiments Using Estuarine Assemblages". Hydrobiologia. 548 (1): 233–249. doi:10.1007/s10750-005-5195-x. ISSN   0018-8158. S2CID   40194710.
  12. ↑ Miller, Carrie J.; Roelke, Daniel L.; Davis, Stephen E.; Li, Hsiu-Ping; Gable, George (2008). "The role of inflow magnitude and frequency on plankton communities from the Guadalupe Estuary, Texas, USA: Findings from microcosm experiments". Estuarine, Coastal and Shelf Science. 80 (1): 67–73. Bibcode:2008ECSS...80...67M. doi:10.1016/j.ecss.2008.07.006.
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